KDM5A_HUMAN
ID KDM5A_HUMAN Reviewed; 1690 AA.
AC P29375; A8MV76; Q4LE72; Q86XZ1;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Lysine-specific demethylase 5A;
DE EC=1.14.11.67 {ECO:0000305|PubMed:17320160, ECO:0000305|PubMed:17320161, ECO:0000305|PubMed:17320163};
DE AltName: Full=Histone demethylase JARID1A;
DE AltName: Full=Jumonji/ARID domain-containing protein 1A;
DE AltName: Full=Retinoblastoma-binding protein 2;
DE Short=RBBP-2;
DE AltName: Full=[histone H3]-trimethyl-L-lysine(4) demethylase 5A {ECO:0000305};
GN Name=KDM5A {ECO:0000312|HGNC:HGNC:9886};
GN Synonyms=JARID1A, RBBP2, RBP2 {ECO:0000303|PubMed:18270511};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH RB1.
RX PubMed=8414517;
RA Fattaey A.R., Helin K., Dembski M.S., Dyson N., Harlow E., Vuocolo G.A.,
RA Hanobik M.G., Haskell K.M., Oliff A., Defeo-Jones D., Jones R.E.;
RT "Characterization of the retinoblastoma binding proteins RBP1 and RBP2.";
RL Oncogene 8:3149-3156(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA Okazaki N., Koga H., Nagase T., Ohara O.;
RT "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT encoding large proteins by the ORF trap cloning method.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1099 (ISOFORMS 1/2).
RC TISSUE=Eye, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1102-1564.
RX PubMed=1857421; DOI=10.1038/352251a0;
RA Defeo-Jones D., Huang P.S., Jones R.E., Haskell K.M., Vuocolo G.A.,
RA Hanobik M.G., Huber H.E., Oliff A.;
RT "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma
RT gene product.";
RL Nature 352:251-254(1991).
RN [6]
RP INTERACTION WITH RB1, AND SUBCELLULAR LOCATION.
RX PubMed=7935440; DOI=10.1128/mcb.14.11.7256-7264.1994;
RA Kim Y.W., Otterson G.A., Kratzke R.A., Coxon A.B., Kaye F.J.;
RT "Differential specificity for binding of retinoblastoma binding protein 2
RT to RB, p107, and TATA-binding protein.";
RL Mol. Cell. Biol. 14:7256-7264(1994).
RN [7]
RP INTERACTION WITH LMO2.
RX PubMed=9129143; DOI=10.1038/sj.onc.1200988;
RA Mao S., Neale G.A.M., Goorha R.M.;
RT "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein
RT 2.";
RL Oncogene 14:1531-1539(1997).
RN [8]
RP FUNCTION, AND INTERACTION WITH ESR1.
RX PubMed=11358960; DOI=10.1074/jbc.m100313200;
RA Chan S.W., Hong W.;
RT "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone
RT receptor-mediated transcription.";
RL J. Biol. Chem. 276:28402-28412(2001).
RN [9]
RP SUBCELLULAR LOCATION, INTERACTION WITH RB1, AND FUNCTION.
RX PubMed=15949438; DOI=10.1016/j.molcel.2005.05.012;
RA Benevolenskaya E.V., Murray H.L., Branton P., Young R.A., Kaelin W.G. Jr.;
RT "Binding of pRB to the PHD protein RBP2 promotes cellular
RT differentiation.";
RL Mol. Cell 18:623-635(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1603, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP FUNCTION.
RX PubMed=17320163; DOI=10.1016/j.cell.2007.02.013;
RA Klose R.J., Yan Q., Tothova Z., Yamane K., Erdjument-Bromage H., Tempst P.,
RA Gilliland D.G., Zhang Y., Kaelin W.G. Jr.;
RT "The retinoblastoma binding protein RBP2 is an H3K4 demethylase.";
RL Cell 128:889-900(2007).
RN [12]
RP FUNCTION.
RX PubMed=17320161; DOI=10.1016/j.cell.2007.02.003;
RA Christensen J., Agger K., Cloos P.A.C., Pasini D., Rose S., Sennels L.,
RA Rappsilber J., Hansen K.H., Salcini A.E., Helin K.;
RT "RBP2 belongs to a family of demethylases, specific for tri-and
RT dimethylated lysine 4 on histone 3.";
RL Cell 128:1063-1076(2007).
RN [13]
RP FUNCTION.
RX PubMed=17320160; DOI=10.1016/j.cell.2007.02.017;
RA Iwase S., Lan F., Bayliss P., de la Torre-Ubieta L., Huarte M., Qi H.H.,
RA Whetstine J.R., Bonni A., Roberts T.M., Shi Y.;
RT "The X-linked mental retardation gene SMCX/JARID1C defines a family of
RT histone H3 lysine 4 demethylases.";
RL Cell 128:1077-1088(2007).
RN [14]
RP INTERACTION WITH MYC AND MYCN.
RX PubMed=17311883; DOI=10.1101/gad.1523007;
RA Secombe J., Li L., Carlos L., Eisenman R.N.;
RT "The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase
RT required for dMyc-induced cell growth.";
RL Genes Dev. 21:537-551(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111 AND SER-1331, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP INTERACTION WITH ARNTL AND CLOCK.
RX PubMed=21960634; DOI=10.1126/science.1206022;
RA DiTacchio L., Le H.D., Vollmers C., Hatori M., Witcher M., Secombe J.,
RA Panda S.;
RT "Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences
RT the circadian clock.";
RL Science 333:1881-1885(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204; SER-1330; SER-1438;
RP SER-1488 AND SER-1666, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-191 AND LYS-1007, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP STRUCTURE BY NMR OF 85-175, FUNCTION, DOMAIN, DNA-BINDING, AND MUTAGENESIS
RP OF ARG-112; LYS-152; SER-156 AND LEU-157.
RX PubMed=18270511; DOI=10.1038/nsmb.1400;
RA Tu S., Teng Y.C., Yuan C., Wu Y.T., Chan M.Y., Cheng A.N., Lin P.H.,
RA Juan L.J., Tsai M.D.;
RT "The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC
RT motif.";
RL Nat. Struct. Mol. Biol. 15:419-421(2008).
RN [23]
RP STRUCTURE BY NMR OF 1609-1659 IN COMPLEX WITH ZINC AND HISTONE H3,
RP STRUCTURE BY X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1609-1659 IN COMPLEX
RP WITH ZINC AND HISTONE H3, FUNCTION, INTERACTION WITH HISTONE H3,
RP MUTAGENESIS OF VAL-1609; TRP-1625 AND 1634-GLU-TRP-1635, AND DOMAIN.
RX PubMed=19430464; DOI=10.1038/nature08036;
RA Wang G.G., Song J., Wang Z., Dormann H.L., Casadio F., Li H., Luo J.L.,
RA Patel D.J., Allis C.D.;
RT "Haematopoietic malignancies caused by dysregulation of a chromatin-binding
RT PHD finger.";
RL Nature 459:847-851(2009).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (3.18 ANGSTROMS) OF 12-797 IN COMPLEX WITH ZINC AND
RP NICKEL.
RX PubMed=27499454; DOI=10.1016/j.bmcl.2016.07.070;
RA Labadie S.S., Dragovich P.S., Cummings R.T., Deshmukh G., Gustafson A.,
RA Han N., Harmange J.C., Kiefer J.R., Li Y., Liang J., Liederer B.M., Liu Y.,
RA Manieri W., Mao W., Murray L., Ortwine D.F., Trojer P., VanderPorten E.,
RA Vinogradova M., Wen L.;
RT "Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.";
RL Bioorg. Med. Chem. Lett. 26:4492-4496(2016).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 1-87 AND 348-588 IN COMPLEX WITH
RP INHIBITORS; MANGANESE AND 2-OXOGLUTARATE, BIOPHYSICOCHEMICAL PROPERTIES,
RP FUNCTION, AND MUTAGENESIS OF CYS-626 AND CYS-636.
RX PubMed=27427228; DOI=10.1016/j.chembiol.2016.06.006;
RA Horton J.R., Liu X., Gale M., Wu L., Shanks J.R., Zhang X., Webber P.J.,
RA Bell J.S., Kales S.C., Mott B.T., Rai G., Jansen D.J., Henderson M.J.,
RA Urban D.J., Hall M.D., Simeonov A., Maloney D.J., Johns M.A., Fu H.,
RA Jadhav A., Vertino P.M., Yan Q., Cheng X.;
RT "Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by
RT Diverse Compounds.";
RL Cell Chem. Biol. 23:769-781(2016).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1-87 AND 348-588 IN COMPLEX WITH
RP MANGANESE AND 2-OXOGLUTARATE.
RX PubMed=26645689; DOI=10.1074/jbc.m115.698449;
RA Horton J.R., Engstrom A., Zoeller E.L., Liu X., Shanks J.R., Zhang X.,
RA Johns M.A., Vertino P.M., Fu H., Cheng X.;
RT "Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of
RT Histone H3 Lysine 4 Demethylases.";
RL J. Biol. Chem. 291:2631-2646(2016).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 12-797 IN COMPLEX WITH AN
RP INHIBITOR ZINC AND NICKEL, AND ACTIVITY REGULATION.
RX PubMed=27214401; DOI=10.1038/nchembio.2085;
RA Vinogradova M., Gehling V.S., Gustafson A., Arora S., Tindell C.A.,
RA Wilson C., Williamson K.E., Guler G.D., Gangurde P., Manieri W., Busby J.,
RA Flynn E.M., Lan F., Kim H.J., Odate S., Cochran A.G., Liu Y.,
RA Wongchenko M., Yang Y., Cheung T.K., Maile T.M., Lau T., Costa M.,
RA Hegde G.V., Jackson E., Pitti R., Arnott D., Bailey C., Bellon S.,
RA Cummings R.T., Albrecht B.K., Harmange J.C., Kiefer J.R., Trojer P.,
RA Classon M.;
RT "An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer
RT cells.";
RL Nat. Chem. Biol. 12:531-538(2016).
RN [28]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=16419055; DOI=10.1002/gcc.20308;
RA van Zutven L.J., Onen E., Velthuizen S.C., van Drunen E., von Bergh A.R.,
RA van den Heuvel-Eibrink M.M., Veronese A., Mecucci C., Negrini M.,
RA de Greef G.E., Beverloo H.B.;
RT "Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13)
RT as a new partner gene.";
RL Genes Chromosomes Cancer 45:437-446(2006).
RN [29]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=23531517; DOI=10.1038/leu.2013.87;
RA de Rooij J.D., Hollink I.H., Arentsen-Peters S.T., van Galen J.F.,
RA Berna Beverloo H., Baruchel A., Trka J., Reinhardt D., Sonneveld E.,
RA Zimmermann M., Alonzo T.A., Pieters R., Meshinchi S.,
RA van den Heuvel-Eibrink M.M., Zwaan C.M.;
RT "NUP98/JARID1A is a novel recurrent abnormality in pediatric acute
RT megakaryoblastic leukemia with a distinct HOX gene expression pattern.";
RL Leukemia 27:2280-2288(2013).
CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-4' of
CC histone H3, thereby playing a central role in histone code. Does not
CC demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79'
CC or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not
CC monomethylated H3 'Lys-4'. Regulates specific gene transcription
CC through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May
CC stimulate transcription mediated by nuclear receptors. Involved in
CC transcriptional regulation of Hox proteins during cell differentiation
CC (PubMed:19430464). May participate in transcriptional repression of
CC cytokines such as CXCL12. Plays a role in the regulation of the
CC circadian rhythm and in maintaining the normal periodicity of the
CC circadian clock. In a histone demethylase-independent manner, acts as a
CC coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional
CC activation of PER1/2 and other clock-controlled genes and increases
CC histone acetylation at PER1/2 promoters by inhibiting the activity of
CC HDAC1 (By similarity). Seems to act as a transcriptional corepressor
CC for some genes such as MT1F and to favor the proliferation of cancer
CC cells (PubMed:27427228). {ECO:0000250|UniProtKB:Q3UXZ9,
CC ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438,
CC ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320161,
CC ECO:0000269|PubMed:17320163, ECO:0000269|PubMed:18270511,
CC ECO:0000269|PubMed:19430464, ECO:0000269|PubMed:27427228}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-
CC [histone H3] + 3 O2 = 3 CO2 + 3 formaldehyde + L-lysyl(4)-[histone
CC H3] + 3 succinate; Xref=Rhea:RHEA:60208, Rhea:RHEA-COMP:15537,
CC Rhea:RHEA-COMP:15547, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61961; EC=1.14.11.67;
CC Evidence={ECO:0000305|PubMed:17320160, ECO:0000305|PubMed:17320161,
CC ECO:0000305|PubMed:17320163};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: The inhibitors KDOAM-25, CPI-455 and others
CC inhibits its demethylase activity, resulting to cell growth arrest in
CC cancer cells. {ECO:0000269|PubMed:27214401,
CC ECO:0000269|PubMed:27427228}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9 uM for 2-oxoglutarate {ECO:0000269|PubMed:27427228};
CC KM=2.9 uM for histone H3K4me3 {ECO:0000269|PubMed:27427228};
CC Note=kcat is 2.1 min(-1) and 1.9 min(-1) for 2-oxoglutarate and
CC histone H3K4me3, respectively. {ECO:0000269|PubMed:27427228};
CC -!- SUBUNIT: Interacts with SUZ12; the interaction is direct (By
CC similarity). Interacts with the viral protein-binding domain of RB1.
CC Interacts with ESR1, MYC, MYCN and LMO2. Interacts with HDAC1; this
CC interaction impairs histone deacetylation by HDAC1 (By similarity).
CC Interacts with ARNTL/BMAL1 and CLOCK. Interacts (via PHD-type 1 zinc
CC finger) with histone H3 unmodified at 'Lys-4' and (via PHD-type 3 zinc
CC finger) with histone H3 di- and trimethylated at 'Lys-4'
CC (PubMed:19430464). {ECO:0000250|UniProtKB:Q3UXZ9,
CC ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438,
CC ECO:0000269|PubMed:17311883, ECO:0000269|PubMed:19430464,
CC ECO:0000269|PubMed:21960634, ECO:0000269|PubMed:7935440,
CC ECO:0000269|PubMed:8414517, ECO:0000269|PubMed:9129143}.
CC -!- INTERACTION:
CC P29375; P06400: RB1; NbExp=2; IntAct=EBI-1560836, EBI-491274;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:15949438,
CC ECO:0000269|PubMed:7935440}. Nucleus {ECO:0000250|UniProtKB:Q3UXZ9}.
CC Note=Occupies promoters of genes involved in RNA metabolism and
CC mitochondrial function. {ECO:0000250|UniProtKB:Q3UXZ9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P29375-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29375-2; Sequence=VSP_035746;
CC -!- DOMAIN: The GSGFP motif is required for the interaction with SUZ12 (By
CC similarity). The ARID domain specifically binds to the CCGCCC motif and
CC is required for the lysine-specific histone demethylase activity
CC (PubMed:18270511). The PHD-type 3 zinc finger is required for the
CC interaction with histone H3 di- and trimethylated at 'Lys-4'
CC (PubMed:19430464). {ECO:0000250|UniProtKB:Q3UXZ9,
CC ECO:0000269|PubMed:18270511, ECO:0000269|PubMed:19430464}.
CC -!- DISEASE: Note=A chromosomal aberration involving KDM5A has been found
CC in M5 type acute myeloid leukemia. Translocation t(11;12)(p15;p13) with
CC NUP98. {ECO:0000269|PubMed:23531517}.
CC -!- DISEASE: Note=Chromosomal aberrations involving KDM5A have been found
CC in M7 type childhood acute myeloid leukemia. Translocation
CC t(11;12)(p15;p13) with NUP98. {ECO:0000269|PubMed:16419055,
CC ECO:0000269|PubMed:23531517}.
CC -!- SIMILARITY: Belongs to the JARID1 histone demethylase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB28544.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE06081.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/JARID1AID41033ch12p13.html";
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DR EMBL; S66431; AAB28544.1; ALT_FRAME; mRNA.
DR EMBL; AB209999; BAE06081.1; ALT_INIT; mRNA.
DR EMBL; AC005844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007406; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048307; AAH48307.1; ALT_TERM; mRNA.
DR EMBL; BC053893; AAH53893.1; ALT_TERM; mRNA.
DR EMBL; BC110916; AAI10917.1; ALT_TERM; mRNA.
DR CCDS; CCDS41736.1; -. [P29375-1]
DR PIR; I78879; I78879.
DR RefSeq; NP_001036068.1; NM_001042603.2. [P29375-1]
DR PDB; 2JXJ; NMR; -; A=85-175.
DR PDB; 2KGG; NMR; -; A=1609-1659.
DR PDB; 2KGI; NMR; -; A=1609-1659.
DR PDB; 3GL6; X-ray; 1.90 A; A=1609-1659.
DR PDB; 5C11; X-ray; 2.80 A; A=1609-1659.
DR PDB; 5CEH; X-ray; 3.14 A; A=12-797.
DR PDB; 5E6H; X-ray; 2.24 A; A=1-87, A=348-588.
DR PDB; 5ISL; X-ray; 1.69 A; A=1-87, A=348-588.
DR PDB; 5IVB; X-ray; 1.39 A; A=1-87, A=348-588.
DR PDB; 5IVC; X-ray; 1.57 A; A=1-87, A=348-588.
DR PDB; 5IVE; X-ray; 1.78 A; A=1-87, A=348-588.
DR PDB; 5IVF; X-ray; 1.68 A; A=1-87, A=348-588.
DR PDB; 5IVJ; X-ray; 1.57 A; A=1-87, A=348-588.
DR PDB; 5IVV; X-ray; 1.85 A; A=1-87, A=348-588.
DR PDB; 5IVY; X-ray; 1.45 A; A=1-87, A=348-588.
DR PDB; 5IW0; X-ray; 1.63 A; A=1-87, A=348-588.
DR PDB; 5IWF; X-ray; 2.29 A; A=1-87, A=348-588.
DR PDB; 5K4L; X-ray; 3.18 A; A/B=12-797.
DR PDB; 5V9P; X-ray; 3.00 A; A=12-797.
DR PDB; 5V9T; X-ray; 3.05 A; A/B=12-797.
DR PDB; 6BGU; X-ray; 1.68 A; A=1-588.
DR PDB; 6BGV; X-ray; 1.59 A; A=1-588.
DR PDB; 6BGW; X-ray; 1.64 A; A=1-588.
DR PDB; 6BGX; X-ray; 1.88 A; A=1-588.
DR PDB; 6BGY; X-ray; 1.22 A; A=1-588.
DR PDB; 6BGZ; X-ray; 1.69 A; A=1-588.
DR PDB; 6BH0; X-ray; 1.99 A; A=1-588.
DR PDB; 6BH1; X-ray; 1.93 A; A=1-588.
DR PDB; 6BH2; X-ray; 1.45 A; A=1-588.
DR PDB; 6BH3; X-ray; 1.70 A; A=1-588.
DR PDB; 6BH4; X-ray; 2.05 A; A=1-588.
DR PDB; 6BH5; X-ray; 1.65 A; A=1-588.
DR PDB; 6DQ4; X-ray; 1.39 A; A=1-588.
DR PDB; 6DQ5; X-ray; 1.89 A; A=1-588.
DR PDB; 6DQ6; X-ray; 1.59 A; A=1-588.
DR PDB; 6DQ7; X-ray; 1.85 A; A=1-588.
DR PDB; 6DQ8; X-ray; 1.46 A; A=1-588.
DR PDB; 6DQ9; X-ray; 1.75 A; A=1-588.
DR PDB; 6DQA; X-ray; 1.89 A; A=1-588.
DR PDB; 6DQB; X-ray; 1.79 A; A=1-588.
DR PDB; 6DQC; X-ray; 1.75 A; A=1-588.
DR PDB; 6DQD; X-ray; 1.99 A; A=1-588.
DR PDB; 6DQE; X-ray; 1.69 A; A=1-588.
DR PDB; 6DQF; X-ray; 1.69 A; A=1-588.
DR PDB; 7KLO; NMR; -; A=287-344.
DR PDB; 7KLR; NMR; -; A=287-344.
DR PDBsum; 2JXJ; -.
DR PDBsum; 2KGG; -.
DR PDBsum; 2KGI; -.
DR PDBsum; 3GL6; -.
DR PDBsum; 5C11; -.
DR PDBsum; 5CEH; -.
DR PDBsum; 5E6H; -.
DR PDBsum; 5ISL; -.
DR PDBsum; 5IVB; -.
DR PDBsum; 5IVC; -.
DR PDBsum; 5IVE; -.
DR PDBsum; 5IVF; -.
DR PDBsum; 5IVJ; -.
DR PDBsum; 5IVV; -.
DR PDBsum; 5IVY; -.
DR PDBsum; 5IW0; -.
DR PDBsum; 5IWF; -.
DR PDBsum; 5K4L; -.
DR PDBsum; 5V9P; -.
DR PDBsum; 5V9T; -.
DR PDBsum; 6BGU; -.
DR PDBsum; 6BGV; -.
DR PDBsum; 6BGW; -.
DR PDBsum; 6BGX; -.
DR PDBsum; 6BGY; -.
DR PDBsum; 6BGZ; -.
DR PDBsum; 6BH0; -.
DR PDBsum; 6BH1; -.
DR PDBsum; 6BH2; -.
DR PDBsum; 6BH3; -.
DR PDBsum; 6BH4; -.
DR PDBsum; 6BH5; -.
DR PDBsum; 6DQ4; -.
DR PDBsum; 6DQ5; -.
DR PDBsum; 6DQ6; -.
DR PDBsum; 6DQ7; -.
DR PDBsum; 6DQ8; -.
DR PDBsum; 6DQ9; -.
DR PDBsum; 6DQA; -.
DR PDBsum; 6DQB; -.
DR PDBsum; 6DQC; -.
DR PDBsum; 6DQD; -.
DR PDBsum; 6DQE; -.
DR PDBsum; 6DQF; -.
DR PDBsum; 7KLO; -.
DR PDBsum; 7KLR; -.
DR AlphaFoldDB; P29375; -.
DR BMRB; P29375; -.
DR SMR; P29375; -.
DR BioGRID; 111862; 54.
DR DIP; DIP-472N; -.
DR IntAct; P29375; 25.
DR MINT; P29375; -.
DR STRING; 9606.ENSP00000382688; -.
DR BindingDB; P29375; -.
DR ChEMBL; CHEMBL2424504; -.
DR GuidetoPHARMACOLOGY; 2680; -.
DR iPTMnet; P29375; -.
DR PhosphoSitePlus; P29375; -.
DR SwissPalm; P29375; -.
DR BioMuta; KDM5A; -.
DR DMDM; 215274124; -.
DR EPD; P29375; -.
DR jPOST; P29375; -.
DR MassIVE; P29375; -.
DR MaxQB; P29375; -.
DR PaxDb; P29375; -.
DR PeptideAtlas; P29375; -.
DR PRIDE; P29375; -.
DR ProteomicsDB; 54559; -. [P29375-1]
DR ProteomicsDB; 54560; -. [P29375-2]
DR Antibodypedia; 1751; 232 antibodies from 28 providers.
DR DNASU; 5927; -.
DR Ensembl; ENST00000399788.7; ENSP00000382688.2; ENSG00000073614.13. [P29375-1]
DR GeneID; 5927; -.
DR KEGG; hsa:5927; -.
DR MANE-Select; ENST00000399788.7; ENSP00000382688.2; NM_001042603.3; NP_001036068.1.
DR UCSC; uc001qif.3; human. [P29375-1]
DR CTD; 5927; -.
DR DisGeNET; 5927; -.
DR GeneCards; KDM5A; -.
DR HGNC; HGNC:9886; KDM5A.
DR HPA; ENSG00000073614; Tissue enhanced (bone).
DR MalaCards; KDM5A; -.
DR MIM; 180202; gene.
DR neXtProt; NX_P29375; -.
DR OpenTargets; ENSG00000073614; -.
DR PharmGKB; PA34250; -.
DR VEuPathDB; HostDB:ENSG00000073614; -.
DR eggNOG; KOG1246; Eukaryota.
DR GeneTree; ENSGT00940000157170; -.
DR HOGENOM; CLU_000991_2_0_1; -.
DR InParanoid; P29375; -.
DR OMA; KWAPVAP; -.
DR OrthoDB; 664180at2759; -.
DR PhylomeDB; P29375; -.
DR TreeFam; TF106476; -.
DR BioCyc; MetaCyc:ENSG00000073614-MON; -.
DR BRENDA; 1.14.11.67; 2681.
DR PathwayCommons; P29375; -.
DR Reactome; R-HSA-3214842; HDMs demethylate histones.
DR SignaLink; P29375; -.
DR SIGNOR; P29375; -.
DR BioGRID-ORCS; 5927; 18 hits in 1121 CRISPR screens.
DR ChiTaRS; KDM5A; human.
DR EvolutionaryTrace; P29375; -.
DR GeneWiki; JARID1A; -.
DR GenomeRNAi; 5927; -.
DR Pharos; P29375; Tchem.
DR PRO; PR:P29375; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P29375; protein.
DR Bgee; ENSG00000073614; Expressed in colonic epithelium and 205 other tissues.
DR ExpressionAtlas; P29375; baseline and differential.
DR Genevisible; P29375; HS.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:CAFA.
DR GO; GO:0032993; C:protein-DNA complex; IEA:Ensembl.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:GDB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0034647; F:histone H3-tri/di/monomethyl-lysine-4 demethylase activity; IDA:CAFA.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:CAFA.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0034720; P:histone H3-K4 demethylation; IDA:CAFA.
DR GO; GO:1901726; P:negative regulation of histone deacetylase activity; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP:CAFA.
DR DisProt; DP02224; -.
DR Gene3D; 1.10.150.60; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR InterPro; IPR001606; ARID_dom.
DR InterPro; IPR036431; ARID_dom_sf.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR003349; JmjN.
DR InterPro; IPR013637; Lys_sp_deMease-like_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR004198; Znf_C5HC2.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01388; ARID; 1.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF02375; JmjN; 1.
DR Pfam; PF00628; PHD; 2.
DR Pfam; PF08429; PLU-1; 1.
DR Pfam; PF02928; zf-C5HC2; 1.
DR SMART; SM00501; BRIGHT; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00545; JmjN; 1.
DR SMART; SM00249; PHD; 3.
DR SUPFAM; SSF46774; SSF46774; 1.
DR SUPFAM; SSF57903; SSF57903; 3.
DR PROSITE; PS51011; ARID; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS51183; JMJN; 1.
DR PROSITE; PS01359; ZF_PHD_1; 2.
DR PROSITE; PS50016; ZF_PHD_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Biological rhythms;
KW Chromatin regulator; Chromosomal rearrangement; Developmental protein;
KW Dioxygenase; Iron; Isopeptide bond; Metal-binding; Nucleus; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1690
FT /note="Lysine-specific demethylase 5A"
FT /id="PRO_0000200584"
FT DOMAIN 19..60
FT /note="JmjN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537"
FT DOMAIN 84..174
FT /note="ARID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00355"
FT DOMAIN 437..603
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 293..343
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 676..728
FT /note="C5HC2"
FT /evidence="ECO:0000269|PubMed:27214401,
FT ECO:0000269|PubMed:27499454, ECO:0007744|PDB:5CEH"
FT ZN_FING 1161..1218
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1607..1661
FT /note="PHD-type 3"
FT /evidence="ECO:0000269|PubMed:19430464"
FT REGION 1327..1348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1407..1433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1490..1509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1516..1543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1623..1690
FT /note="Interaction with LMO2"
FT /evidence="ECO:0000269|PubMed:9129143"
FT MOTIF 419..423
FT /note="GSGFP motif"
FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9"
FT BINDING 409
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:26645689,
FT ECO:0000269|PubMed:27427228"
FT BINDING 483
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000305|PubMed:26645689, ECO:0000305|PubMed:27214401,
FT ECO:0000305|PubMed:27427228, ECO:0000305|PubMed:27499454"
FT BINDING 485
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:26645689,
FT ECO:0000305|PubMed:27214401, ECO:0000305|PubMed:27427228,
FT ECO:0000305|PubMed:27499454"
FT BINDING 491
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:26645689,
FT ECO:0000269|PubMed:27427228"
FT BINDING 493
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:26645689,
FT ECO:0000269|PubMed:27427228"
FT BINDING 501
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:26645689,
FT ECO:0000269|PubMed:27427228"
FT BINDING 571
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000305|PubMed:26645689, ECO:0000305|PubMed:27214401,
FT ECO:0000305|PubMed:27427228, ECO:0000305|PubMed:27499454"
FT SITE 1485..1486
FT /note="Breakpoint for translocation to form the NUP98-KDM5A
FT fusion protein"
FT /evidence="ECO:0000269|PubMed:16419055"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1343
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9"
FT MOD_RES 1345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9"
FT MOD_RES 1438
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1595
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9"
FT MOD_RES 1598
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 1603
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 1666
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 191
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1007
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1623..1690
FT /note="VDWVQCDGGCDEWFHQVCVGVSPEMAENEDYICINCAKKQGPVSPGPAPPPS
FT FIMSYKLPMEDLKETS -> GVVFVTEEERDKKY (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8414517"
FT /id="VSP_035746"
FT VARIANT 865
FT /note="M -> T (in dbSNP:rs11062385)"
FT /id="VAR_032984"
FT VARIANT 1190
FT /note="P -> A (in dbSNP:rs2229353)"
FT /id="VAR_032985"
FT MUTAGEN 112
FT /note="R->E: Decreases DNA-binding."
FT /evidence="ECO:0000269|PubMed:18270511"
FT MUTAGEN 152
FT /note="K->E: Abolishes DNA-binding."
FT /evidence="ECO:0000269|PubMed:18270511"
FT MUTAGEN 156
FT /note="S->D: Decreases DNA-binding."
FT /evidence="ECO:0000269|PubMed:18270511"
FT MUTAGEN 157
FT /note="L->E: Decreases DNA-binding."
FT /evidence="ECO:0000269|PubMed:18270511"
FT MUTAGEN 626
FT /note="C->S: No effect on lysine-specific histone
FT demethylase activity; when associated with S-636."
FT /evidence="ECO:0000269|PubMed:27427228"
FT MUTAGEN 636
FT /note="C->S: No effect on lysine-specific histone
FT demethylase activity; when associated with S-626."
FT /evidence="ECO:0000269|PubMed:27427228"
FT MUTAGEN 1609
FT /note="V->G: No effect on interaction with histone H3
FT di- and trimethylated at 'Lys-4'."
FT /evidence="ECO:0000269|PubMed:19430464"
FT MUTAGEN 1625
FT /note="W->A: Abolishes interaction with histone H3 di- and
FT trimethylated at 'Lys-4'."
FT /evidence="ECO:0000269|PubMed:19430464"
FT MUTAGEN 1634..1635
FT /note="EW->AA: Abolishes interaction with histone H3
FT di- and trimethylated at 'Lys-4'."
FT /evidence="ECO:0000269|PubMed:19430464"
FT CONFLICT 1411
FT /note="Q -> QVFFGK (in Ref. 1; AAB28544)"
FT /evidence="ECO:0000305"
FT CONFLICT 1547
FT /note="E -> K (in Ref. 1; AAB28544)"
FT /evidence="ECO:0000305"
FT CONFLICT 1612..1614
FT /note="AQN -> EPD (in Ref. 1; AAB28544)"
FT /evidence="ECO:0000305"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 32..43
FT /evidence="ECO:0007829|PDB:6BGY"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:6BGY"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:6BGY"
FT TURN 77..82
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 85..100
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 154..173
FT /evidence="ECO:0007829|PDB:5V9P"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:5V9T"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:7KLO"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:7KLR"
FT HELIX 305..307
FT /evidence="ECO:0007829|PDB:7KLO"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:7KLR"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:7KLO"
FT STRAND 323..326
FT /evidence="ECO:0007829|PDB:7KLR"
FT HELIX 338..342
FT /evidence="ECO:0007829|PDB:7KLO"
FT TURN 350..353
FT /evidence="ECO:0007829|PDB:6DQ4"
FT HELIX 363..378
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 387..399
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:5E6H"
FT STRAND 406..414
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 415..418
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 426..429
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 436..440
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 455..459
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 465..468
FT /evidence="ECO:0007829|PDB:5V9T"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 490..499
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 501..506
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 511..521
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 531..534
FT /evidence="ECO:0007829|PDB:6BGY"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:6BGV"
FT HELIX 542..547
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 553..557
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 562..565
FT /evidence="ECO:0007829|PDB:6BGY"
FT STRAND 570..586
FT /evidence="ECO:0007829|PDB:6BGY"
FT HELIX 589..591
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 592..604
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 613..621
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 629..655
FT /evidence="ECO:0007829|PDB:5V9P"
FT STRAND 661..663
FT /evidence="ECO:0007829|PDB:5K4L"
FT HELIX 666..668
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 671..673
FT /evidence="ECO:0007829|PDB:5V9P"
FT STRAND 674..676
FT /evidence="ECO:0007829|PDB:5V9T"
FT STRAND 685..688
FT /evidence="ECO:0007829|PDB:5V9P"
FT STRAND 691..693
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 703..705
FT /evidence="ECO:0007829|PDB:5CEH"
FT STRAND 711..713
FT /evidence="ECO:0007829|PDB:5CEH"
FT STRAND 716..720
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 724..743
FT /evidence="ECO:0007829|PDB:5V9P"
FT HELIX 766..772
FT /evidence="ECO:0007829|PDB:5V9P"
FT TURN 780..784
FT /evidence="ECO:0007829|PDB:5V9P"
FT STRAND 1620..1627
FT /evidence="ECO:0007829|PDB:3GL6"
FT STRAND 1629..1632
FT /evidence="ECO:0007829|PDB:3GL6"
FT STRAND 1635..1637
FT /evidence="ECO:0007829|PDB:3GL6"
FT HELIX 1639..1641
FT /evidence="ECO:0007829|PDB:3GL6"
FT HELIX 1645..1650
FT /evidence="ECO:0007829|PDB:3GL6"
FT TURN 1656..1658
FT /evidence="ECO:0007829|PDB:3GL6"
SQ SEQUENCE 1690 AA; 192095 MW; FCF6DC22DEF001DF CRC64;
MAGVGPGGYA AEFVPPPECP VFEPSWEEFT DPLSFIGRIR PLAEKTGICK IRPPKDWQPP
FACEVKSFRF TPRVQRLNEL EAMTRVRLDF LDQLAKFWEL QGSTLKIPVV ERKILDLYAL
SKIVASKGGF EMVTKEKKWS KVGSRLGYLP GKGTGSLLKS HYERILYPYE LFQSGVSLMG
VQMPNLDLKE KVEPEVLSTD TQTSPEPGTR MNILPKRTRR VKTQSESGDV SRNTELKKLQ
IFGAGPKVVG LAMGTKDKED EVTRRRKVTN RSDAFNMQMR QRKGTLSVNF VDLYVCMFCG
RGNNEDKLLL CDGCDDSYHT FCLIPPLPDV PKGDWRCPKC VAEECSKPRE AFGFEQAVRE
YTLQSFGEMA DNFKSDYFNM PVHMVPTELV EKEFWRLVSS IEEDVIVEYG ADISSKDFGS
GFPVKDGRRK ILPEEEEYAL SGWNLNNMPV LEQSVLAHIN VDISGMKVPW LYVGMCFSSF
CWHIEDHWSY SINYLHWGEP KTWYGVPSHA AEQLEEVMRE LAPELFESQP DLLHQLVTIM
NPNVLMEHGV PVYRTNQCAG EFVVTFPRAY HSGFNQGYNF AEAVNFCTAD WLPIGRQCVN
HYRRLRRHCV FSHEELIFKM AADPECLDVG LAAMVCKELT LMTEEETRLR ESVVQMGVLM
SEEEVFELVP DDERQCSACR TTCFLSALTC SCNPERLVCL YHPTDLCPCP MQKKCLRYRY
PLEDLPSLLY GVKVRAQSYD TWVSRVTEAL SANFNHKKDL IELRVMLEDA EDRKYPENDL
FRKLRDAVKE AETCASVAQL LLSKKQKHRQ SPDSGRTRTK LTVEELKAFV QQLFSLPCVI
SQARQVKNLL DDVEEFHERA QEAMMDETPD SSKLQMLIDM GSSLYVELPE LPRLKQELQQ
ARWLDEVRLT LSDPQQVTLD VMKKLIDSGV GLAPHHAVEK AMAELQELLT VSERWEEKAK
VCLQARPRHS VASLESIVNE AKNIPAFLPN VLSLKEALQK AREWTAKVEA IQSGSNYAYL
EQLESLSAKG RPIPVRLEAL PQVESQVAAA RAWRERTGRT FLKKNSSHTL LQVLSPRTDI
GVYGSGKNRR KKVKELIEKE KEKDLDLEPL SDLEEGLEET RDTAMVVAVF KEREQKEIEA
MHSLRAANLA KMTMVDRIEE VKFCICRKTA SGFMLQCELC KDWFHNSCVP LPKSSSQKKG
SSWQAKEVKF LCPLCMRSRR PRLETILSLL VSLQKLPVRL PEGEALQCLT ERAMSWQDRA
RQALATDELS SALAKLSVLS QRMVEQAARE KTEKIISAEL QKAAANPDLQ GHLPSFQQSA
FNRVVSSVSS SPRQTMDYDD EETDSDEDIR ETYGYDMKDT ASVKSSSSLE PNLFCDEEIP
IKSEEVVTHM WTAPSFCAEH AYSSASKSCS QGSSTPRKQP RKSPLVPRSL EPPVLELSPG
AKAQLEELMM VGDLLEVSLD ETQHIWRILQ ATHPPSEDRF LHIMEDDSME EKPLKVKGKD
SSEKKRKRKL EKVEQLFGEG KQKSKELKKM DKPRKKKLKL GADKSKELNK LAKKLAKEEE
RKKKKEKAAA AKVELVKEST EKKREKKVLD IPSKYDWSGA EESDDENAVC AAQNCQRPCK
DKVDWVQCDG GCDEWFHQVC VGVSPEMAEN EDYICINCAK KQGPVSPGPA PPPSFIMSYK
LPMEDLKETS
